Mechanistic Contribution of Internal Circadian Misalignment to the Cardiometabolic Risk of Sleep Loss

/ABSTRACT Over one in three Americans regularly sleep less than the recommended 7 hours per night and thus obtain insufficient sleep. Compared to adults who maintain adequate sleep durations, adults who maintain insufficient sleep are at higher risk of developing obesity and type 2 diabetes (T2D). Furthermore, experimentally imposed sleep restriction in otherwise healthy adults can impair insulin sensitivity to levels commonly observed in people with pre-diabetes or in aging. Given the strength of this rigorous body of evidence, clinical guidelines recommend “healthy sleep” to help prevent and manage cardiometabolic disease. However, effective interventions to increase sleep duration and mitigate the adverse cardiometabolic risk of insufficient sleep are limited. Moreover, achieving adequate sleep may be impractical for many people like medical and military personnel, emergency responders, shift workers, and students. Thus, interventions that mitigate the adverse cardiometabolic risk of insufficient sleep, even when sleep loss is unavoidable, could have significant public health benefits. A key barrier limiting the development of such interventions is that the precise physiological mechanisms mediating the adverse cardiometabolic risk of insufficient sleep remain unclear. One understudied and potentially modifiable mechanism contributing to the adverse cardiometabolic risk of insufficient sleep is circadian misalignment. Specifically, our preliminary data strongly suggest late night light exposure and food intake during sleep loss cause an internal misalignment of central and peripheral circadian rhythms, which is a fundamental mechanism contributing to the adverse cardiometabolic risk of sleep loss. We therefore hypothesize that preventing both light exposure and food intake from occurring during the circadian biological night will prevent internal circadian misalignment during sleep loss, and thereby mitigate the adverse cardiometabolic risk of short sleep duration. To test this hypothesis, we will conduct a randomized cross-over laboratory trial to systematically examine the mechanistic contributions of delayed timing of light exposure and food intake to (1) internal circadian misalignment, (2) impaired insulin sensitivity, and (3) excess energy intake during experimental sleep loss. We expect our findings will advance the field by providing valuable insights into physiological mechanisms that mediate risk of obesity and T2D among people with insufficient sleep. Such knowledge will create the foundation to design novel interventions focused on optimizing the timing of light and food intake to improve cardiometabolic health in people with insufficient sleep. These interventions may be especially beneficial in scenarios where sleep loss is unavoidable, ultimately helping to improve health and quality of life among people with insufficient sleep. Project Number: 1R01HL178934-01 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Christopher Depner | Institution: UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH, SALT LAKE CITY, UT | Award Amount: $730,993 | Activity Code: R01 | Study Section: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01HL17893401